Disappointing results from several HIV prevention trials have raised questions about the feasibility of future microbicide trials, including the extent to which the selectivity of trial participants, adherence to study protocols and the reliability and validity of self-reported behavioral data undermine researchers'ability to detect efficacy. In collaboration with YRG CARE, a leading Indian research institution based in Chennai, the ultimate goal of this project is to help determine whether it would be fruitful and feasible to conduct an expanded Phase 2 or Phase 3 clinical trial of a Population Council second-generation microbicide in southern India. Through four experiments we will identify behavioral and social factors that may affect the successful implementation of microbicide trials. The specific aims are to: 1. Evaluate how sex workers who participate in a four month simulated microbicide trial of a placebo gel differ from their peers who are unwilling to participate with survey data obtained through respondent driven sampling (RDS), an innovative technique to generate a representative sample of hidden and hard-to-reach populations;2. Assess whether surveys, rather than the conventional facility-based strategy, are feasible for recruiting trial participants;3. Investigate rates of HIV and other sexually transmitted infections, including HSV-2 and gonorrhea among women who enroll in the simulated microbicide trial;4. Compare adherence and high risk behavior among participants in the simulated trial using a variety of innovative research tools tested within an experimental framework;5. Explore if prior knowledge of biomarkers affects gel adherence and/or self-reports of sexual activity, gel and condom use;6. Determine whether audio computer assisted self-interviewing yields more accurate reports than computer assisted personal interviewing for the collection of behavioral data. This research will lead to the development of a set of recommendations for the design and implementation of future microbicide trials in India and elsewhere.